# Leveraging Zika virus and the immune system to treat glioblastoma

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $389,854

## Abstract

PROJECT SUMMARY
Glioblastoma (GBM) is a brain tumor that causes neurological deterioration and death in most patients within 2
years. Despite aggressive therapy, most GBMs reappear within 6 months. A major reason for this outcome is
because GBM stem cells (GSCs) are resistant to existing therapies. Currently, no treatment consistently kills
these highly resistant cells. However, the Zika virus epidemic has provided us with a new approach to eradicate
GSCs. ZIKV targets normal stem cells in the developing fetal brain, yet has minimal effects on differentiated
neurons or the adult brain. Since GSCs share properties with neural stem cells, we investigated whether the
natural honing and lytic activity of ZIKV could be harnessed to target and kill GSCs. We published the first use
of ZIKV to kill GSCs. We showed that ZIKV kills GSCs in tumors removed from patients, with minimal impact on
non-GSC tumor cells, called differentiated GBM cells. Importantly, normal human brain cells were not affected
by ZIKV. After intracranial treatment with ZIKV, mice harboring gliomas survived more than twice as long as
untreated mice and, in some cases, treated mice were long-term survivors. In addition to the resistance of GBM
stem cell to chemoradiation, GBM is the hallmark example of an immunotherapy-resistant tumor. Importantly,
we found that in vivo, ZIKV treatment reduces tumor size and extends survival beyond that expected for only
anti-GSC effects. This suggested that ZIKV killing of GSCs may trigger an immune response against the
remainder of the tumor. In more recent studies, we have found that CD8+ T cells are required for the efficacy of
ZIKV as an oncolytic therapy in vivo. Our central hypothesis is that ZIKV elicits an anti-tumor immune response
that could be made even more effective by combining it with existing immunotherapies. Aim 1 will determine how
CD8+ T cells promote tumor clearance after ZIKV and Aim 2 will determine whether ZIKV can be combined with
immunotherapy or standard-of-care for GBM to improve outcomes. Our long-term goal is to develop a new
treatment for GBM by leveraging the immune system response to ZIKV.

## Key facts

- **NIH application ID:** 10121169
- **Project number:** 1R01NS117149-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Milan Girish Chheda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $389,854
- **Award type:** 1
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121169

## Citation

> US National Institutes of Health, RePORTER application 10121169, Leveraging Zika virus and the immune system to treat glioblastoma (1R01NS117149-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10121169. Licensed CC0.

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